The close approach of cells to surfaces.
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Biomedical subjects
Publications and source records attributed to E F Leonard.
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Numerous factors that influence sodium handling have been identified, and many have been studied in minute detail; however, relatively little information is available regarding either the steady-state relationship between dietary sodium intake and sodium stores or the transient response of intact animals to challenges to sodium homeostasis. In this paper the principles of elementary feedback control theory have been used both to obtain and analyze quantitative models of the feedback control of sodium stores. It has been assumed that the sodium content of the body determines the rate of urinary sodium excretion, and a mass balance has been used to obtain differential equations that describe the dynamics of sodium stores. Both first- and second-order models are considered, and their predictions for both steady states and transients are compared critically with observations from the literature, using data from human studies whenever possible. The results indicate that a relatively simple proportional feedback controller describes most available data well; however, gaps in the available information are identified, and opportunities for future experimental investigation are described.
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Graph theory methods were used to analyze the topology of the renal glomerular capillary network using data both from a serial reconstruction of a rat glomerulus and from the literature. The graphs obtained were tested for planarity, and all but one were found to be nonplanar. This result indicated that the development of the glomerular capillary network must include a nonplanar growth process, and new growth models were proposed. In addition, the statistical properties of capillary branching patterns were analyzed, and a node degree distribution function estimate was obtained.
The potential utility of glycerol as an osmotic agent for peritoneal dialysis was evaluated by conducting both isosmotic and hyperosmotic exchanges in anesthetized rats. Similar exchanges were conducted using glucose, and the results with the two agents were compared. During hyperosmotic exchanges both agents produced significant osmotic flow of water, but at initial molar concentrations that were equal the flow observed with glycerol was nearly 40% less than that observed with glucose. The lower volume transport generated by glycerol was found to be due to its surprisingly rapid removal from peritoneal fluid when it was present at hyperosmotic concentrations, but paradoxically during isosmotic exchanges, when its concentration was low, glycerol was absorbed only slightly faster than glucose. The observed increase in peritoneal permeability when glycerol was used resulted in a twofold increase in the caloric load imposed per unit of water removed in comparison with glucose.
Solutions of hemoglobin have often been considered for both hypothermic and normothermic perfusion of isolated kidneys. This paper considers basic issues, preparative techniques, and the viscosity of hemoglobin solutions, as well as the demands made by the kidney on a perfusate. The natural system of oxygen transport in higher animals is complex, and its perturbation to produce convenient hemoglobin-based renal perfusates produces numerous problems. The desirable effect of 2,3-diphosphoglycerate is not easily maintained in a perfusate, but its inclusion can be avoided by appropriate choice of species donating hemoglobin. Hemoglobin tetramer in free solution may dissociate and be lost by glomerular filtration. Ferric hemoglobin, the dominant form at redox equilibrium, is useless for oxygen transport; the ferrous form is maintained in the erythrocyte by reducing metabolites and, under normothermic conditions, the ferrous to ferric conversion is slow but significant. Methods for lysis of erythrocytes and removal of their stroma are discussed; reduction of ferric hemoglobin by chemical agents and electrolysis are considered in detail; and means for adjusting concentration and solute background are presented. The need for carbonic anhydrase in hemoglobin solutions used as perfusates is shown and methods for its provision are discussed. A review of viscometric data for hemoglobin solutions is provided to which original data are added. Hemoglobin solutions show a temperature-independent intrinsic viscosity, according to Einstein's theory for a molecule of 23 A radius. The O2 and CO2 transport requirements of renal perfusates are analyzed comprehensively. The normothermic kidney has an unusual respiration pattern, requiring an amount of oxygen that is not fixed but, rather, proportional to the total blood flow rate. In canines the average arterio-venous O2 content difference found by many investigators is 2.14 vol%; the corresponding CO2 value is 2.47 vol%; and the respiratory quotient is greater than unity. Wide limits of PO2, but not P CO2 in perfusate, appear allowable. A final section evaluates hemoglobin solutions as both normothermic and hypothermic renal perfusates from the viewpoints of blood gas chemistry, urinary loss, oncotic pressure, fatty acid carrying capacity, viscosity, and the need for functions usually attributed to platelets. It is concluded, overall, that perfusates containing free hemoglobin have only a limited role to play in renal perfusion.
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Evaluation of blood oxygenators using whole blood is inconvenient and expensive, although it is the ultimate preclinical test. Sodium sulfite solutions have advantages over blood for studying oxygen uptake: They are inexpensive, fewer variables need control, and deoxygenation is unnecessary. Assays and interpretation of results are easy. The kinetics of sulfite oxidation must be fast and the concentration of sulfite must be low to emulate oxygen uptake by blood. The kinetics were studied yielding a first order rate constant in sulfite, zero order in oxygen, of 740/min. Limitations of the technique were evaluated using the experimental rate constant and an adaptation of Lightfoot's approximation. While the reaction of hemoglobin is reversible and essentially instantaneous, that for sulfite is irreversible and finite. Thus if the approach to saturation is not monotonic or if the mass transfer resistance is significantly lowered, e.g., when blood film thicknesses are thinner than a few hundred microns, deviations may occur. Two TMO oxygenators and several prototypes were tested, with both sulfite and bovine blood. Uptakes of oxygen were comparable and the effect of parameter variations were similar. The use of sulfite for early evaluation of oxygenators is concluded to be very useful.
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In the study of interactions of blood with artificial surfaces, it is common practice to wet these surfaces with a saline solution before exposing them to blood. The effect of this procedure on subsequent adhesion of blood platelets has been investigated both theoretically and experimentally, with a spinning disc apparatus. A large part of the observed delay in the initiation of platelet adhesion when using this apparatus is attributed to the time involved in displacing the prewetting fluid and bringing platelets near the surface. This observation is relevant to speculations of other researchers about the time course of adhesion-related reactions at the surface-proper. Other theoretical solutions are developed for the transient Leveque problem, which relates to a uniform shear-flow near a surface, and for a stagnation point apparatus. These solutions are compared with delay effects noticed in experimental data published by others.
Factors determining thrombus formation on a foreign surface were studied with the use of plastic flow chambers introduced into extracorporeal shunts. Silicone rubber shunts, joining the carotid artery and jugular vein, were implanted in dogs and remained patent for several weeks. The flow chamber geometry consisted of a 4.8 mm diameter straight tube having a 3.2 X 3.2 mm circumferential cavity in the wall. Chambers were introduced sequentially into the shunts for exposure times of 10 to 30 minutes and regulated blood flow rates of 100 to 400 ml/min. The dry weight of thrombus accumulated in the chamber (5 to 50 mg) was found to increase with exposure time up to 20 minutes and to decrease with increasing flow rate. Various components of the process of thrombus formation were altered by the administration of acetylsalicylic acid, heparin and lysozyme, used alone and in pairs. Heparin was found to be the most effective antithrombotic agent, dry weights of accumulated thrombus being on the order of 50 percent lower when compared to control values. The efficacy of heparin was found to be unaffected by the presence of aspirin and lysozyme, which themselves were not effective antithrombotic agents under the conditions of these experiments. The technique described here may provide a useful animal model for studying the influence of blood flow and different biomaterials on thrombus formation.
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